Toward the Selective Inhibition of G Proteins: Total Synthesis of a Simplified YM-254890 Analog

  • Org Lett. 2015 May 1;17(9):2270-3. doi: 10.1021/acs.orglett.5b00944.
Derek T Rensing  1 ,  Sakshi Uppal  1 ,  Kendall J Blumer  2 ,  Kevin D Moeller  1
Affiliations
  • 1. †Department of Chemistry, Washington University, St. Louis, Missouri 63130, United States.
  • 2. ‡Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, United States.
PMID: 25875152 DOI: 10.1021/acs.orglett.5b00944
Abstract

A simplified analog (WU-07047) of the selective Gαq/11 inhibitor YM-254890 has been synthesized, and an initial probe of its activity conducted. In the analog, the two peptide-based linkers in the cyclic YM-254890 have been replaced with hydrocarbon chains. This enables a convergent approach to the synthesis of the analog. Biochemical assays showed that while the simplified analog is not as potent as YM-254890, it does still inhibit Gq.

Products